目的 基于超高效液相色譜-四級桿飛行時間串聯(lián)質譜法（UPLC-Q-TOF-MS/MS）分析商陸水提物的化學成分，并結合網(wǎng)絡毒理學和分子對接方法預測商陸致肝損傷的毒性成分和潛在的作用靶點及通路。方法 根據(jù)色譜峰保留時間、精確相對分子質量、二級質譜裂解碎片等信息，并結合文獻數(shù)據(jù)，對商陸水提物化學成分進行分析鑒定。通過Swiss TargetPrediction、TCMSP、ETCM和BATMAN-TCM數(shù)據(jù)庫預測商陸成分靶點；通過CTD和GeneCards數(shù)據(jù)庫篩選肝損傷靶點；采用String數(shù)據(jù)庫和Cytoscape 3.7.1軟件構建蛋白質相互作用（PPI）網(wǎng)絡，并篩選核心靶點；利用Metascape數(shù)據(jù)庫對核心靶點進行基因本體（GO）注釋和京都基因與基因組百科全書（KEGG）通路富集分析；應用Cytoscape 3.7.1軟件構建“成分-核心靶點-通路”網(wǎng)絡，并篩選核心成分。通過AutoDock Vina 1.2.0軟件對核心成分和核心靶點進行分子對接驗證。結果 利用UPLC-Q-TOF-MS/MS法從商陸水提物中共鑒定出40個化學成分，主要為三萜皂苷類及少量黃酮、酚酸、揮發(fā)油等。共獲得101個共有靶點，篩選出26個核心靶點，包括ALB、TNF、AKT1等；涉及通路包括HIF-1信號通路、MAPK信號通路、PI3K-Akt信號通路、TNF信號通路等，與炎癥、肝細胞凋亡、肝纖維化途徑密切相關。篩選到6個核心成分進行分子對接，結果顯示，美商陸苷F、美商陸皂苷元、商陸皂苷A、商陸皂苷元、山柰酚3-O-α-L-鼠李吡喃糖基（1→2）-β-D-吡喃葡萄糖苷及芥子酸與ALB、TNF、AKTI等靶點蛋白具有良好的結合活性。結論 商陸在大劑量使用時可能具有潛在的肝毒性，推測主要毒性成分可能為三萜皂苷類，通過促進炎癥發(fā)生、調控肝纖維化進程、誘導肝細胞凋亡途徑導致肝損傷。

Objective To analyze the chemical components of Phytolaccae Radix based on ultra performance liquid chromatographyquadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). And to predict the toxic components, potential targets and pathways of liver injury induced by Phytolaccae Radix based on network toxicology and molecular docking. Methods According to the retention time of chromatographic peak, accurate molecular weight and fragmentation information of secondary mass spectrometry, combined with the literature data, the chemical components of Phytolaccae Radix were analyzed and identified. The component targets of Phytolaccae Radix were predict by Swiss Target Prediction, TCMSP, ETCM and BATMAN-TCM Database. The liver injury targets were screened by CTD and GeneCards databases. By using String database and Cytoscape 3.7.1 software, PPI network was constructed and core targets were screened. By using Metascape database, Gene Ontology (GO) annotation and KEGG pathway enrichment were analyzed of core targets. Cytoscape 3.7.1 software was used to construct the "component-core target-pathway" network and screen the core components. The molecular docking verification of core components and core targets was performed by AutoDock Vina 1.2.0 software. Results A total of 40 chemical components were identified from the aqueous extract of Phytolaccae Radix, mainly triterpenoid saponins, and a small amount of flavonoids, phenolic acids, volatile oil. A total of 101 common targets were obtained, and 26 core targets were screened, including ALB, TNF, AKT1, etc. The pathways involved include HIF-1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway and so on, which are closely related to inflammation, hepatocyte apoptosis and hepatic fibrosis. Six core components were screened for molecular docking. The results showed that phytolaccoside F, phytolaccagenin, esculentoside A, esculentagenin, kaempferol 3-O-alpha-L-rhamnopyranosyl (1→2)-beta-D-glucopyranoside and sinapic acid had good binding activities with ALB, TNF, AKT1 and other target proteins. Conclusion Phytolaccae Radix may have potential hepatotoxicity when used in large doses. It is speculated that the main toxic components may be triterpenoid saponins, which play a role in liver injury by promoting inflammation, regulating liver fibrosis, and inducing hepatocyte apoptosis.

R994

國家自然科學基金資助項目（82173955）